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Women living with HIV (WLWH) are at an increased risk of developing HPV-related high grade cervical dysplasia and cervical cancer. Prior World Health Organization (WHO) screening guidelines recommended starting screening at age 30. We assessed characteristics of women diagnosed with cervical cancer to further inform and refine screening guidelines. We prospectively enrolled women diagnosed with cervical cancer from January 2015 to March 2020 at two tertiary hospitals in Gaborone, Botswana. We performed chi-square and ANOVA analyses to evaluate the association between age upon diagnosis and HIV status, CD4 count, viral load, and other sociodemographic and clinical factors. Data were available for 1130 women who were diagnosed with cervical cancer and 69.3% were WLWH. The median age overall was 47.9 (IQR 41.2-59.1), 44.6 IQR: 39.8 - 50.9) among WLWH, and 61.2 (IQR 48.6-69.3) among women living without HIV. There were 1.3% of women aged <30 years old, 19.1% were 30-39 and 37.2% were 40-49. Overall, 20.4% (n = 231) of cancers were in women <40 years. Age of cervical cancer diagnosis is younger in countries with higher HIV prevalence, like Botswana. Approximately 20% of the patients presented with cancer at <40 years of age and would have likely benefited from screening 10 years prior to cancer diagnosis to provide an opportunity for detection and treatment of pre-invasive disease., Competing Interests: Declaration of Competing Interest Authors do not have any conflicts of interest to disclose., (Copyright © 2023. Published by Elsevier Ltd.)

Objective: To determine the prevalence and predictors of precancerous cervical lesions among HIV-positive women in Jos, Nigeria., Methods: A cross-sectional study was conducted from October 2017 to January 2018 among 326 HIV-positive women. Cervical smears were collected for examination at the AIDS Preventive Initiative of Nigeria clinics of Jos University Teaching Hospital (JUTH) and Bingham University Teaching Hospital (BhUTH), Jos, Nigeria. Demographic characteristics of participants were documented using a structured questionnaire. Data were entered and analyzed using SPSS version 21., Results: Of the 326 participants, precancerous cervical lesions were present in 40 (12.2%) women: 4 (1.2%) had atypical squamous cells of undetermined significance, 19 (5.8%) had low-grade squamous intraepithelial lesions, 1 (0.3%) had atypical squamous cells cannot exclude high-grade squamous intraepithelial lesions, 13 (4.0%) had high-grade squamous intraepithelial lesions, and 3 (0.9%) had high-grade squamous intraepithelial lesions, suspected for invasion. The multivariate logistics regression model showed that parity (odds ratio 3.4, 95% confidence interval 1.3-9.5, P=0.043) was a significant predictor of precancerous cervical lesions., Conclusion: The prevalence of precancerous cervical lesions among HIV-infected women is relatively low compared to earlier reported prevalence in an HIV population in Jos. Increasing parity was a significant predictor., (© 2020 International Federation of Gynecology and Obstetrics.)

Background: Women living with HIV (WLWH) are at increased risk of persistent human papillomavirus (HPV) infection, cervical dysplasia and cervical cancer compared with women from the general population (WGP). We assessed the prevalence and distribution of cervical high-risk (hr) HPV infection and cytological abnormalities in WLWH compared with WGP in Denmark. Predictors of HPV and cytological abnormalities were estimated in WLWH., Methods: WLWH consecutively enrolled in the Study on HIV, cervical Abnormalities and infections in women in Denmark (SHADE) in 2011 and were examined for cervical HPV and cytological abnormalities. WLWH were matched on age and prior cytological findings with WGP from an earlier study. HIV demographics were retrieved from the nationwide Danish HIV Cohort Study. Logistic regression was used to estimate predictors of hrHPV and cytological abnormalities., Results: Of 334 included WLWH 26.4 % were positive for hrHPV as opposed to 16.6 % WGP (p < 0.0001). WLWH had a higher number of multiple infections (>1 h genotype present) (38.5 % versus 25.7 %, p = 0.030). Hr genotypes in descending order of frequency were HPV58 (7.1 %), 52 (5.4 %), and 16 (4.8 %) in WLWH versus HPV16 (4.1 %), 52 (2.8 %) and 58 (2.4 %) in WGP. Predictors of hrHPV in WLWH were short duration of HAART (adjusted OR per year 0.90 (95 % CI 0.84-0.96)), AIDS prior to inclusion (adjusted OR 3.61 (95 % CI 1.75-7.46)), ≥5 lifetime sexual partners (adjusted OR 2.20 (95 % CI 1.08-4.49)), sexual debut <16 years of age (adjusted OR 2.05 (95 % CI 1.03-4.10)) and CD4 < 350 cells/μL (adjusted OR 2.53 (95 % CI 1.20-5.40)). Cytological abnormalities were prevalent in 10.4 % vs. 5.2 % (p = 0.0003) of WLWH and WGP. In WLWH with hrHPV, short duration of HAART predicted cervical dysplasia (adjusted OR per year 0.83 (95 % CI 0.71-0.97))., Conclusions: WLWH presented with more cervical hrHPV infections and cytological abnormalities, and a different distribution of hrHPV genotypes compared with WGP. Cervical hrHPV and cytological abnormalities were predicted by short duration of HAART.

Background: Few data exist regarding the effect of hormonal contraception (HC) on incidence and progression of cervical disease (e.g., cervical dysplasia, squamous intraepithelial lesions, cervical intraepithelial neoplasia) in HIV-infected African women., Study Design: We conducted an observational study of HIV-seropositive women in Johannesburg, South Africa. The effect of individual HC types on the incidence and progression of cervical disease was determined using Poisson regression to obtain adjusted incidence rate ratios., Results: We evaluated 594 HIV-infected women, with median follow-up time of 445 days; 75 of these women were receiving some form of HC (largely DMPA, NET-EN, or COCs) at baseline. Risks of incidence and progression of cervical disease were similar comparing women not receiving HCs to women receiving DMPA, NET-EN, or COCs both individually by HC-type and considering all HC together., Conclusions: There was no statistically significant effect of particular HC methods or of HC use in general on rates of incidence or progression of cervical disease in this study. These results should reassure us that use of HC is unlikely to substantially increase risks of cervical disease among HIV-positive women., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Background: Facing the dual burden of invasive cervical cancer and HIV in sub-Saharan Africa, the identification of preventable determinants of Cervical Intraepithelial Neoplasia (CIN) in HIV-infected women is of paramount importance., Methods: A cervical cancer screening based on visual inspection methods was proposed to HIV-infected women in care in Abidjan, Côte d'Ivoire. Positively screened women were referred for a colposcopy to a gynaecologist who performed directed biopsies., Results: Of the 2,998 HIV-infected women enrolled, 132 (4.4%) CIN of any grade (CIN+) were identified. Women had been followed-up for a median duration of three years [IQR: 1-5] and 76% were on antiretroviral treatment (ART). Their median most recent CD4 count was 452 [IQR: 301-621] cells/mm3. In multivariate analysis, CIN+ was associated with a most recent CD4 count >350 cells/mm3 (OR: 0.3; 95% CI: 0.2-0.6) or ≥200-350 cells/mm3 (OR 0.6; 95% CI 0.4-1.0) (Ref: <200 cells/mm3 CD4) (p<10-4)., Conclusions: The presence of CIN+ is less common among HIV-infected women with limited or no immune deficiency. Despite the potential impact of immunological recovery on the reduction of premalignant cervical lesions through the use of ART, cervical cancer prevention, including screening and vaccination remains a priority in West Africa while ART is rolled-out.

Background: To study the prevalence of abnormal anal cytology by Papanicolaou (Pap) technique in HIV- infected women who attended a HIV clinic at Prapokklao Hospital, Chanthaburi, Thailand., Materials and Methods: HIV-infected women who attended a HIV clinic at Prapokklao Hospital from March 2013 to February 2014 were recruited for anal Pap smears. Participants who had abnormal results of equally or over "abnormal squamous/glandular cells of undetermined significance" (ASC-US) were classified as abnormal anal cytology., Results: A total of 590 anal Pap smears were performed at HIV clinic of Prapokklao Hospital during the study period. There were only 13 patients who had abnormal Pap tests, which were: 11 ASC-US and 2 HSIL (high grade squamous intraepithelial lesion). The prevalence of abnormal anal Pap smears in HIV-infected women who attended HIV clinic at Prapokklao Hospital was 2.2 percent. Percentage of high risk HPV in patients who had abnormal Pap test was 88.9 (8/9)., Conclusions: The prevalence of abnormal anal Papanicolaou smears in HIV-infected women who attended the HIV clinic at Prapokklao hospital was quite low in comparison to the earlier literature.

Background: The purpose of this study was to determine proportional rates of cervical precancerous lesions and cancer, and associations with socio-demographic variables, HIV status, and CD4 cell count., Materials and Methods: A retrospective comparative study was conducted targeting the medical records of all women over age 18 that were diagnosed histologically through colposcopy with cervical precancerous lesions and cancer from 1 December 2011 to 30 November 2012., Results: A total of 313 patient records were used for data analysis. The average age was 39.1 (SD=2.04) years. More than a third (37.1%) of the patients had CIN III or cervical cancer. There was a significant association between age, CD4 cell count, HIV status, and cervical lesions (p<0.05). Age was found to be an influential predictor of cervical lesions (OR=0.67, 95%CI: 0.46-0.98)., Conclusions: There exists an association between age and cervical lesions, with presentation of cervical precancerous lesions and cervical cancer at a younger age among HIV reactive patients. The National Guidelines should be brought in line with the National HIV Counseling and Testing Policy to offer Pap smears to all sexually active women that test HIV reactive during routine HIV Testing.

Objective: Local immunity plays an important role in the cervical defense mechanisms that prevent the development of cervical intraepithelial neoplasia. The objective of this study was to determine the involvement of local immunity by evaluating Langerhans cell (LC) density in cervical biopsies of human immunodeficiency virus (HIV)-positive and HIV-negative women., Materials and Methods: A cross-sectional study was developed by including HIV-positive and HIV-negative women. All patients presented human papillomavirus DNA from the uterine cervix, which was detected by polymerase chain reaction or hybrid capture II. Cervical biopsies were assessed for LC density and cervical intraepithelial neoplasia. Langerhans cells were identified by immunohistochemistry using anti-CD1a and anti-S100 antibodies. Associations among cervical LC density, the type of cervical lesion, CD4 lymphocyte count, and HIV viral load were analyzed using logistic regression (SPSS, version 12.0)., Results: Seventy-seven women (40 seropositive and 37 seronegative) were enrolled. The mean ± SD LC density identified with the anti-CD1a antibody was 0.80 ± 0.7 cells versus 2.6 ± 1.6 cells (P < 0.0001), whereas the mean ± SD LC density identified by the anti-S100 antibody was 1.3 ± 1.0 cells versus 3.6 ± 1.7 cells (P < 0.0001) among the HIV-positive and HIV-negative women, respectively. There were no associations between LC density and HIV viral load, CD4 lymphocyte count, or human papillomavirus genotype (P > 0.05). In a logistic regression model, HIV infection was the only factor independently associated with a decrease in LC density., Conclusions: Human immunodeficiency virus infection was found to be an independent factor that explains the decrease in local immunity in the uterine cervix, which could allow the development of cervical lesions. This effect was not associated with CD4 lymphocyte count or HIV viral load.

Objective: To estimate the accuracy of Pap testing for women who are human immunodeficiency virus (HIV)-seropositive, with a focus on negative predictive value., Methods: Participants in the Women's Interagency HIV Study were monitored with conventional Pap tests every 6 months. After excluding those with abnormal Pap test results before study, cervical disease, or hysterectomy, women with negative enrollment Pap test results were monitored for development of precancer within 15 or 39 months, defined as a Pap test result read as high-grade squamous intraepithelial lesion, atypical glandular cells favor neoplasia, or adenocarcinoma in situ, or a cervical biopsy read as cervical intraepithelial neoplasia 2 or worse. Correlations between one or more consecutive negative Pap test results and subsequent precancer were assessed using Cox proportional hazards models., Results: Among 942 HIV-infected women with negative baseline Pap test results, eight (1%) developed precancer within 15 months and 40 (4%) within 39 months. After three consecutive negative Pap test results, precancer was rare, with no cases within 15 months and 10 of 539 (2%) within 39 months. No women developed precancer or cancer within 39 months after 10 consecutive negative Pap test results. Risks for precancer within 15 months after negative Pap test result included current smoking (adjusted hazard ratio [HR] 1.5, 95% confidence interval [CI] 1.2-2.0 compared with nonsmokers), younger age (adjusted HR 1.5, 95% CI 1.1-2.1 for women aged younger than 31 years compared with older than 45 years), and lower CD4 count (adjusted HR 11.8, 95% CI 1.3-2.3 for CD4 200-500/microliter, adjusted HR 2.2, 95% CI 1.6-2.9 for CD4 less than 200/microliter, compared with CD4 more than 500/microliter)., Conclusion: Annual Pap testing appears safe for women infected with HIV; for those with serial negative tests, longer intervals are appropriate., Level of Evidence: II.

Background: The distribution of HPV genotypes, their association with rigorously confirmed cervical precancer endpoints, and factors associated with HPV infection have not been previously documented among HIV-infected women in India. We conducted an observational study to expand this evidence base in this population at high risk of cervical cancer., Methods: HIV-infected women (N = 278) in Pune, India underwent HPV genotyping by Linear Array assay. Cervical intraepithelial neoplasia (CIN) disease ascertainment was maximized by detailed assessment using cytology, colposcopy, and histopathology and a composite endpoint., Results: CIN2+ was detected in 11.2% while CIN3 was present in 4.7% participants. HPV genotypes were present in 52.5% (146/278) and 'carcinogenic' HPV genotypes were present in 35.3% (98/278) HIV-infected women. 'Possibly carcinogenic' and 'non/unknown carcinogenic' HPV genotypes were present in 14.7% and 29.5% participants respectively. Multiple (≥ 2) HPV genotypes were present in half (50.7%) of women with HPV, while multiple 'carcinogenic' HPV genotypes were present in just over a quarter (27.8%) of women with 'carcinogenic' HPV. HPV16 was the commonest genotype, present in 12% overall, as well as in 47% and 50% in CIN2+ and CIN3 lesions with a single carcinogenic HPV infection, respectively. The carcinogenic HPV genotypes in declining order of prevalence overall included HPV 16, 56, 18, 39, 35, 51, 31, 59, 33, 58, 68, 45 and 52. Factors independently associated with 'carcinogenic' HPV type detection were reporting ≥ 2 lifetime sexual partners and having lower CD4+ count. HPV16 detection was associated with lower CD4+ cell counts and currently receiving combination antiretroviral therapy., Conclusion: HPV16 was the most common HPV genotype, although a wide diversity and high multiplicity of HPV genotypes was observed. Type-specific attribution of carcinogenic HPV genotypes in CIN3 lesions in HIV-infected women, and etiologic significance of concurrently present non/unknown carcinogenic HPV genotypes await larger studies.

Objectives: To determine the prevalence of HPV and cervical neoplasia among HIV-infected women in southwestern China., Methods: Cervical cytology, HPV detection by Hybrid Capture-2™ assay, and diagnostic colposcopy were followed by cervical biopsy if indicated. Logistic regression analysis was used to analyze associations between HPV co-infection and cervical intraepithelial neoplasia (CIN), and HIV-related clinical and laboratory parameters., Results: Colposcopic-histopathologically proven CIN2+ lesions were present in 7/83 (8.4%) HIV-infected women. Nearly half (41/83, 43%) were co-infected with carcinogenic HPV genotypes. HPV co-infection was higher in women with colposcopic-histopathologically proven CIN2+ lesions than women with

With heterosexual transmission becoming the primary mode of transmission, more women are being infected with human immunodeficiency virus (HIV). Accrued data from around the world indicate that these HIV-infected women exhibit higher rates of persistent HPV infection with multiple oncogenic viruses, more abnormal Pap tests, more prevalent cervical intraepithelial neoplasia (CIN) lesions, and aggressive invasive cervical cancer compared with their HIV-negative counterparts. In countries where HAART was introduced more than a decade ago, HPV-related disease is increasing among ageing HIV-positive women. The high rate of cervical disease seen in HIV-positive women has prompted recommendations for more aggressive surveillance. The best strategy to screen HIV-infected women, particularly in resource-poor nations, remains challenging. This article reviews the collective literature regarding HIV and squamous lesions of the cervix and highlights these key issues., (Copyright © 2010 Wiley-Liss, Inc.)

Introduction: An increasing number of HIV-1-infected women reaches the age of menopause. This infection is associated with a higher incidence of cervical squamous intraepithelial lesions (low-grade or LSIL, high grade or HSIL). The aim of our study was to describe the cervical disease in these patients during menopause., Patients and Methods: Retrospective study, identifying all Pap smears and colposcopy in HIV-1-infected postmenopausal women between 1995 and 2008, in our hospital., Results: Eighteen postmenopausal women, aged of 54 years (43-63), have HIV-1 infection since 7.5 years (2-25). Fifty-one pathological exams were reviewed in which 27 (50.98%) abnormal, including four (7.84%) ASC-US, 15 (29.41%) LSIL lesions, and seven (13.73%) HSIL. Ten patients had surgery (laser, conisation, hysterectomy) during the period. The evolution of cervical lesions was: stability in 40.48%, regression in 35.71% and progression in 23.81%. The median time to develop an HSIL at menopause was 5 years., Conclusion: In our study, postmenopausal HIV-1-infected women have most frequently LSIL and persistent. Monitoring of these postmenopausal women should be continued, the attitude to realise an initial HPV typing and confirmation of an abnormal annually Pap smear with colposcopic exam should be confirmed by larger study., (Copyright © 2010 Elsevier Masson SAS. All rights reserved.)

Context and Objective: The human immunodeficiency virus (HIV) is frequently associated with high-grade intraepithelial neoplasia. Immunosuppression and high HIV viral load are the main risk factors for cervical intraepithelial neoplasia (CIN). The aim of this study was to determine the prevalence of CIN in HIV-infected women in Salvador, Bahia, Brazil, and to describe the risk factors in comparison with non-infected women., Design and Setting: Cross-sectional study at the AIDS Reference Center of Bahia and the Gynecological Outpatient Clinic of Fundação Bahiana para o Desenvolvimento da Ciência, in Salvador, Bahia, Brazil., Methods: Sixty-four HIV-infected women and 76 uninfected women from Salvador were enrolled between May 2006 and May 2007. Associations between CIN and presence of HIV infection, HIV viral load, proportion of T CD4+ lymphocytes and risk factors were evaluated. The independence of the risk factors was investigated using logistic regression., Results: CIN was more prevalent among HIV-infected women than in the control group (26.6% versus 6.6%; P = 0.01). The odds ratio for CIN among HIV-infected women was 3.7 (95% confidence interval, CI: 1.23-11; P = 0.01), after adjusting for the following variables: age at first sexual intercourse, number of partners, number of deliveries and previous history of sexually transmitted disease., Conclusion: The prevalence of CIN among HIV-infected women was significantly higher than among women without HIV infection. HIV infection was the most important risk factor associated with the development of cervical lesions.

Purpose of Review: Cervical cancer, caused by the human papillomavirus (HPV), is the only cancer that is almost preventable through regular screening. In high-resource, as in low-resource and middle-resource countries, women hit by the AIDS epidemic have a high prevalence of infection with HPV and related disease, including cervical cancer. The question whether cervical screening, which helped to reduce dramatically cervical cancer rates through the detection of precancerous lesions in the general population, is as efficient in the setting of HIV is still debated., Recent Findings: The risk for cervical cancer remained high and stable during the last decade in HIV-infected women, and incidence did not decrease with improving CD4 cell counts in women receiving antiviral therapy. Optimal methods to improve both the sensitivity and the specificity of cervical cancer screening are currently evaluated. The use of HPV DNA tests in primary screening endorsed in the general population may be less specific in immunocompromised women and might thus not be as efficient on screening. HPV vaccines, recently available, have no therapeutic effect and might thus not be very useful in preventing cervical cancer in a population highly infected with multiple and persistent HPV., Summary: Cervical cancer prevention remains an important goal in HIV-infected women and specific guidelines are warranted for this increasing population.

The objective of this study was to review the literature on the epidemiological association between human papillomavirus (HPV), HIV, and cervical neoplasia, and the impact of highly active antiretroviral therapy (HAART) on this association. MEDLINE was searched using the terms 'human papillomavirus', 'HPV', 'HIV', 'cervix', 'neoplasm', and 'antiretroviral' to identify articles published before December 2006. HIV-infection was strongly associated with a higher prevalence, incidence, and persistence of HPV infection and correlated with prevalence, incidence, persistence, and progression of squamous intraepithelial lesions. The association between HIV and invasive cervical carcinoma has been more difficult to establish, but is now fully recognized. HAART seems to have little, if any, beneficial effect on the natural history of intraepithelial lesions in HIV-positive women. Despite this fact, HAART, does increase the life expectancy of HIV-positive women. Therefore, it remains important to closely monitor HPV-related disease in women with HIV who are receiving HAART, particularly in regions of the world where cervical screening is not available routinely.

Background: There are over four million people living with HIV/AIDS in Nigeria. Cervical cancer is the most common genital cancer in Nigeria. There are many reports on the association of HIV with increased risk of cervical dysplasia., Objective: To determine the prevalence of abormal cervical smears in Nigerian women who are HIV positive in Lagos., Methods: Cervical smears were taken from 233 HIV positive women and 235 HIV negative women who attended the HIV clinic and the family planning clinic respectively of the Lagos University Teaching Hospital during the period January-April 2004. Proportions were compared with the X2 test., Results: Data were complete for analysis in 227 of HIV positive and 228 of HIV negative women. Mean (SD) ages of HIV positive and HIV negative patients were respectively 35.2 (9.81) and 34.5 (7.37) years. Prevalence of squamous intraepithelial lesion (SIL) was higher in those who were HIV positive than in those who were HIV negative, 10.9% vs 4.3% (X2, 7.04; p=0.00798). Prevalence of high grade SIL was higher in HIV positive than HIV negative subjects, 7.9% vs 2.6% (X2, 6.38; p=0.0115). There was no significant difference in the prevalence of inflammatory smears, 15.7% in HIV positive vs 16.2% in HIV negative., Conclusion: Prevalence of cervical dysplasia is high in women who harbour HIV.

Background and Aim of the Work: The purpose of our study was to determine whether highly active antiretroviral therapy (HAART) reduces the onset of cervical intraepithelial neoplasia (CIN) in HIV-positive women., Methods: The study was designed to assess CIN incidence in a cohort of 101 HIV-positive women and to evaluate its relationship with ongoing antiretroviral therapy. The patients were screened through a combined Pap smear and colposcopic examination on a yearly basis. If any abnormalities were reported, the patients underwent targeted biopsy with histological confirmation of the diagnosis., Results: During the follow-up period, 38 patients (37.6%) developed histologically verified CIN, including low-grade CIN in seven patients (6.9%) and high-grade CIN in 31 patients (30.4%). Over the study period, 43 patients (42.6%) were treated with HAART for at least 6 months, the average duration of treatment being 37 months. Analysis of HAART efficacy in preventing CIN onset, determined by the Cox regression model with a time-dependent covariate adjusted for the CD4 level at the first visit, showed that HAART significantly reduced the risk of developing CIN (hazard ratio, 0.3; p = 0.004)., Conclusion: HIV-positive patients present a high incidence of CIN and of high-grade CIN in particular. HAART exhibits a protective action against the onset of cervical lesions.

Objectives: HIV-infected women living in resource-constrained nations like Zambia are now accessing antiretroviral therapy and thus may live long enough for HPV-induced cervical cancer to manifest and progress. We evaluated the prevalence and predictors of cervical squamous intraepithelial lesions (SIL) among HIV-infected women in Zambia., Methods: We screened 150 consecutive, non-pregnant HIV-infected women accessing HIV/AIDS care services in Lusaka, Zambia. We collected cervical specimens for cytological analysis by liquid-based monolayer cytology (ThinPrep Pap Test) and HPV typing using the Roche Linear Array PCR assay., Results: The median age of study participants was 36 years (range 23-49 years) and their median CD4+ count was 165/microL (range 7-942). The prevalence of SIL on cytology was 76% (114/150), of which 23.3% (35/150) women had low-grade SIL, 32.6% (49/150) had high-grade SIL, and 20% (30/150) had lesions suspicious for squamous cell carcinoma (SCC). High-risk HPV types were present in 85.3% (128/150) women. On univariate analyses, age of the participant, CD4+ cell count, and presence of any high-risk HPV type were significantly associated with the presence of severely abnormal cytological lesions (i.e., high-grade SIL and lesions suspicious for SCC). Multivariable logistic regression modeling suggested the presence of any high-risk HPV type as an independent predictor of severely abnormal cytology (adjusted OR: 12.4, 95% CI 2.62-58.1, p=0.02)., Conclusions: The high prevalence of abnormal squamous cytology in our study is one of the highest reported in any population worldwide. Screening of HIV-infected women in resource-constrained settings like Zambia should be implemented to prevent development of HPV-induced SCC.

HIV-infected women have high risk for precancerous lesions of the uterine cervix. We studied the prevalence and risk factors of squamous intraepithelial lesions (SIL) among systematically followed HIV-infected women enrolled from a population with low HIV prevalence. The study population consisted of 108 HIV-infected women enrolled between 1989 and 2003 with a mean follow-up 4.4 years. Risk factors of SIL were assessed based on samples collected during 2000-02. The overall rates of atypical glandular cells of uncertain significance (AGUS), atypical squamous cells of uncertain significance (ASCUS), low-grade SIL (LSIL) and high-grade SIL (HSIL) were 4, 24, 15 and 5%, respectively. Reduced CD4-lymphocyte count was associated with an increased prevalence of SIL, whereas duration of HIV infection (< or > or =5 years), use of antiretroviral medication, or HIV viral load (<50 or > or =50 copies/mL) was not. The cumulative risk of developing SIL after 1 and 5 years was 17% (95% confidence interval [CI] 7-27%) and 48% (95% CI 33-63%), respectively. The cumulative risk of SIL was increased among women younger than 31 years (P = 0.04) as well as in women displaying high initial HIV viral load (P = 0.01). Our results from a low HIV-incidence population re-emphasize the importance of guidelines for cytologic screening of HIV-seropositive women.

HIV-infected men who have sex with men remain at high risk of developing anal cancer despite the widespread use of highly active antiretroviral therapy (HAART). In HIV-infected women, however, there is some evidence that HAART may be associated with regression of human papillomavirus (HPV)-related cervical disease. So far, epidemiologic data provided by cancer registries have shown no reduction in the incidence of cervical and anal cancer in patients with HIV infection since the initiation of HAART in 1996. Recent data suggest that HPV infection occurs in the anal canal of immunocompromised patients, as an opportunistic infection, in the absence of receptive anal intercourse. Taken together, these lines of evidence support the need for developing anal and cervical cancer screening programs for patients with HIV, whether untreated or on HAART.

Background: The risk of developing the human papillomavirus (HPV)-associated precancer high-grade squamous intraepithelial lesion (HSIL) in human immunodeficiency virus (HIV)-infected adolescents is unknown. We examined the risk of developing HSIL among adolescents with and without HIV infection., Methods: HIV-infected (n = 172) and -uninfected (n = 84) girls aged 13-18 years who were participating in a multicenter study of primarily horizontally acquired HIV infections in adolescents (Reaching for Excellence in Adolescent Health Care) and who did not have HSIL on cytologic examination at study entry or at the first follow-up visit were followed at 6-month intervals. HIV-uninfected girls were recruited for comparison in a 2:1 ratio (HIV infected:HIV uninfected). The primary outcome was cytologic diagnosis of HSIL confirmed by expert review., Results: Incidence of HSIL by the end of follow-up was higher for HIV-infected girls than for HIV-uninfected girls (21.5% vs. 4.8%, respectively). In multivariate analysis, use of hormonal (either estrogen/progesterone oral combination or medroxyprogesterone acetate intramuscular) contraceptives, high cervical mucous concentrations of interleukin (IL)-12, a positive HPV test, and persistent low-grade squamous intraepithelial lesion (LSIL) were significantly associated with the development of HSIL., Conclusions: The incidence of HSIL was alarmingly high in HIV-infected adolescent girls. However, when other predictors were considered in multivariate analysis, HIV status was not retained in the model. The heightened risk for HSIL associated with persistent LSIL underscores the need to closely monitor HIV-infected adolescents with LSIL. The risk for HSIL associated with high concentrations of IL-12 may be suggestive of a local immune dysregulation. The role of hormonal contraception as a risk factor deserves further investigation., (Copyright 2004 Infectious Diseases Society of America)

Objective: To examine the imprint of liquid-based technologies for cervicovaginal cytology on HIV-positive women, who are at high risk for cervical intraepithelial neoplasia., Study Design: We performed a retrospective search of the cytopathology files of Johns Hopkins Hospital for the cervicovaginal cytology of HIV-positive women to examine the effect of liquid-based technology on this population., Results: Significant intraepithelial lesions (SILs) (low grade SIL or greater) were identified in 24% of the conventional smears and 23% of the liquid-based cytology. Atypical squamous cells of undetermined significance (ASCUS)/atypical glandular cells of undetermined significance was diagnosed in 15% of the conventional smears and 9% of the liquid-based preparations (P = .02). In patients with ASCUS diagnoses and tissue follow-up within 7 months, significant SILs were identified in 29% with conventional smears and in 65% with liquid-based cytology., Conclusion: There was no statistically significant difference in the rate of SILs between conventional smears and liquid-based cervicovaginal preparations in HIV-positive women. The diagnosis of ASCUS on liquid-based cytology may have an increased likelihood of representing a significant SIL in comparison to conventional smears. For the high-risk, HIV-positive population, immediate colposcopy and biopsy may be warranted following ASCUS diagnoses on liquid-based cytology.

Objectives: In women with HIV-associated immunosuppression, HPV infections have an increased risk of progression to high-grade cervical intraepithelial neoplasia (CIN). With the HAART-induced prolonged survival and more protracted clinical course of AIDS, progression of CIN to cervical cancer (CC) has become a clinically relevant issue, and the mechanisms responsible for HIV-HPV interactions need further elucidation. The study design and analysis of the baseline data of our new project are presented., Material and Methods: This project is a combination of a prospective cohort study of HIV- and HIV+ women, and a retrospective analysis of CIN lesions and cervical cancer. Up to the present, 244 women have been enrolled (17 HIV+) and subjected to epidemiological interview, colposcopic examination, sampling for HPV testing and typing (PCR, InnoLiPA), and HPV serology. The retrospective series of biopsies were analysed for 13 biomarkers (monitoring key molecular events) using immunohistochemistry and tested for HPV by PCR and TaqMan., Results: HIV- and HIV+ women differ in their exposure status to many of the key epidemiological risk factors of cervical cancer, the most significant ones being number of sexual partners (p = 0.0001), age at onset of sexual activity (p = 0.002), and contraception (yes-no) (p = 0.009). The differences in the baseline clinical observations are less dramatic; HIV-positive women had more frequent HSIL PAP tests (p = 0.040), CIN2 or higher in cervical biopsy (p = 0.049), and external genital warts (p = 0.019). The factors predicting intermediate endpoint markers of cervical cancer, i.e., HSIL PAP smear, ATZ2 in colposcopy, and high-grade CIN in biopsy were analysed in univariate and multivariate regression models. All factors significant in univariate analysis were entered in the multivariate model; HIV-status and Pap smear history maintained their independent predictive power of the HSIL Pap test. The most powerful predictor of ATZ2 colposcopy was HSIL in Pap test. Only the HSIL Pap test and ATZ2 colposcopy remained significant independent predictors of high-grade CIN (p = 0.0001 and p = 0.008, respectively) in the multivariate model., Conclusions: The three intermediate endpoint markers are closely interrelated, but predicted in part by different covariantes in the causal pathway to cervical cancer. To elucidate whether the increased risk of HIV-positive women to high-grade CIN is due a) to their different exposure status to the risk factors, b) to the direct effects of HIV, or c) to molecular interactions between HIV and HPV, we need to complete these analyses separately in HIV+ and HIV- women.

Objective: Human immunodeficiency virus (HIV)-infected women are at risk for cervical intraepithelial neoplasia (CIN) and cancer due to impaired immunosurveillance over human papillomavirus (HPV) infection. Life stress has been implicated in immune decrements in HIV-infected individuals and therefore may contribute to CIN progression over time. The purpose of this study was to determine whether life stress was associated with progression and/or persistence of squamous intraepithelial lesions (SIL), the cytologic diagnosis conferred by Papanicolaou smear, after 1-year follow-up among women co-infected with HIV and HPV., Method: Thirty-two HIV-infected African-American and Caribbean-American women underwent a psychosocial interview, blood draw, colposcopy, and HPV cervical swab at study entry. Using medical chart review, we then abstracted SIL diagnoses at study entry and after 1-year follow-up., Results: Hierarchical logistic regression analysis revealed that higher life stress increased the odds of developing progressive/persistent SIL over 1 year by approximately seven-fold after covarying relevant biological and behavioral control variables., Conclusions: These findings suggest that life stress may constitute an independent risk factor for SIL progression and/or persistence in HIV-infected women. Stress management interventions may decrease risk for SIL progression/persistence in women living with HIV.

A cross-sectional study was conducted on women attending family planning clinics in Harare, Zimbabwe to determine the prevalence of cervical neoplasia among HIV-1 positive women relative to an HIV-1 negative control group. Five hundred and fifty four women were recruited and the prevalence of HIV-1 was 36.8%. Cervical cytology was abnormal in 25.6% of HIV-infected women compared to only 6.7% HIV-1 seronegative women. Cervical neoplasia was significantly associated with HIV infection (chi(2)=42.4, P<0.001). Cellular changes typical of HPV infection (koilocytocis) were recorded in 6.4% of HIV infected women compared with 1.7% of HIV-1-uninfected women (chi(2)=8.43, P=0.004). HIV-1-positive women had twice the risk of having abnormal cervical cells than HIV-negative women (relative risk 2.47, odds ratio 10.14, P<0.001). Therefore the introduction of national cervical screening programme in HIV-1 endemic countries like Zimbabwe where the highest burden of pre-malignant lesions is among HIV-1-infected women needs careful planning because these women have other competing health needs including high rates of opportunistic infections.

Background: To determine: 1) whether the pathology correlates with the degree of immunosuppression, 2) whether there is a relation between pathology and antiretroviral therapies, 3) whether Papanicolau (Pap) smears correlate with colposcopic and histologic findings, 4) whether there is rapid genital disease progression after standard gynaecologic care., Methods: Retrospective study. Immunologic, gynaecologic and virologic data were extracted either from patients charts or from laboratory testing., Results: At first visit Pap smears resulted normal in 43.7% of the women, 8.4% of the patients had reactive and reparative changes, 2.8% atypical cells of undetermined significance, 33.8% low-grade squamous intraepithelial lesions and 11.3% high-grade squamous intraepithelial lesions. Patients with a normal PAP smear had higher CD4 cell count (318+/-191 cells/mL) compared to patients with squamous intraepithelial lesions (297+/-116 cells/mL) but the difference was not statistically significant (Mann-Whitney test). The distribution of cervical dysplasia was found to be similar regardless of antiretroviral therapy (chi(2) test). The sensitivity and specificity of Pap tests for detecting CIN were 94 and 80%. Twenty-two per cent of surgically treated women had persistent or recurrent disease., Conclusions: Lower CD4+ cell counts are not predictive of the presence of cervical dysplasia. All HIV-infected women, independently from their immunological and clinical conditions, need regular Pap smears with appropriate follow-up for abnormal cervicovaginal cytology, this could prevent nearly all deaths from cervical cancer.

Objective: The purpose of this study was to describe the prevalence of human papillomavirus infection and the likelihood of human papillomavirus expression and Papanicolaou test abnormalities among women who have and who are at risk of having human immunodeficiency virus infection., Study Design: Cross-sectional analysis of 767 women who had human immunodeficiency virus infection and 390 women who were at risk of having human immunodeficiency virus infection in 4 cities in the United States., Results: Women who were infected with human immunodeficiency virus were more likely than women who were not infected to have human papillomavirus infection (prevalence ratio, 2.3; 95% CI, 2.0-2.8) but had similar human papillomavirus types. Among women who tested positive for human papillomavirus by polymerase chain reaction, human immunodeficiency virus infection was associated with a high level of human papillomavirus expression (prevalence ratio, 1.3-1.6) and multiple human papillomavirus infections (prevalence ratio, 1.9). However, among women with a high level of human papillomavirus expression or infection with multiple types, there was no association between human immunodeficiency virus serostatus and risk of cervical dysplasia., Conclusion: Through its association with a high level of expression and multiple human papillomavirus infections, human immunodeficiency virus infection may increase the risk of cervical dysplasia in women who are infected with human papillomavirus.

To date the management of HIV-positive women regarding the prevention of cervical cancer remains controversial. There are different approaches to cervical screening in different health authorities in the UK and worldwide due to different funding and healthcare provision in general, the official disease prevalence and the attempt to tailor the screening programme according to a perceived risk for the population covered, but most of all in the diverse evidence provided to aid the development of a screening programme. The advent of high active antiretroviral therapy (HAART) may also have altered the natural history of cervical intraepithelial neoplasia (CIN) before it became sufficiently understood and future studies have to take this into account when investigating the impact of human papillomavirus (HPV) and CIN on the risk of developing cervical cancer. This article aims to summarize the available evidence to date and provide a basis on which an effective and acceptable screening programme for HIV-positive women can be developed.

Increased risk for cervical intraepithelial neoplasia (CIN) in human immunodeficiency virus (HIV)-infected women may be explained by repeated positivity of human papillomavirus (HPV) infection facilitated by HIV infection and related immunosuppression. As part of a longitudinal study with semiannual examinations, 268 women in Baltimore, Maryland (of whom 184 were HIV+), provided 1,426 cervicovaginal lavage specimens tested for HPV DNA by a polymerase chain reaction-based assay between 1992 and 1998. HPV positivity and time to HPV clearance according to HIV serostatus and CD4+ cell count were compared using models for correlated binary data and survival analysis. Of the 187 participants who had at least one positive measurement, the probability of subsequent HPV positivity among HIV- women and HIV+ women with CD4+ > or =200 and <200 cells/microl was 47.5%, 78.7%, and 92.9% (p < 0.001). Within-women HPV results were correlated (i.e., clustered) in each group (p < 0.01). Compared with HIV-participants, the relative incidence of HPV clearance was 0.29 and 0.10 among HIV+ women with CD4+ > or =200 and <200 cells/microl (p < 0.001). At the end of follow-up, 11 women had biopsy-confirmed CIN. The association of HIV and CIN (p = 0.014) was fully explained by repeated HPV positivity induced by HIV infection (p = 0.648). Reversal of immunosuppression following potent antiretroviral therapy must be expected to have a dramatic impact on HIV-related CIN.

Despite advances in antiretroviral therapy and in the treatment and prevention of opportunistic infections, oncological and consequent hematologic complications of human immunodeficiency virus (HIV) infection continue to occur and are of significant clinical importance. Virus-related tumors (e.g., Kaposi's sarcoma, induced by human herpesvirus 8; non-Hodgkin's lymphoma, linked to Epstein-Barr virus; and anogenital tumors, linked to human papillomavirus) are frequent in patients with HIV-induced immune deficiency. The incidence of AIDS-related Kaposi's sarcoma has declined among homosexual men, but this tumor remains problematic in many patients. Non-Hodgkin's lymphoma is 60 times more prevalent in HIV-positive persons than in others and typically presents as advanced-stage, high- or intermediate-grade B cell lymphoma, with frequent extranodal involvement. Primary central nervous system lymphoma is also common. Cervical carcinoma in HIV-positive women is also usually advanced at diagnosis. Anal carcinoma is increasing in both HIV-positive and HIV-negative populations. Chemotherapy for these tumors can result in dose-limiting cytopenia that can be well-controlled with hematopoietic growth factors, allowing patients to avoid transfusions and maintain the dose intensity of their chemotherapy regimens.

The devastating effects of HIV infection in women can be altered dramatically with new therapies. Certain clinical syndromes, including oral thrush, diffuse lymphadenopathy, wasting, unexplained fevers, or oral hairy leukoplakia, clearly indicate a need for HIV testing. This article reviews other clinical syndromes, both gender-specific and non-gender-specific, that may prompt the practitioner to consider HIV testing.

Our study assessed the factors associated with cervical squamous intra-epithelial lesions (SILs) and invasive cervical cancer, with special attention to human immunodeficiency virus (HIV) and human papillomavirus (HPV) infections. Women from 3 outpatient gynecology clinics of Abidjan, Côte d'Ivoire, were screened for cervical abnormalities: 151 women with low-grade SILs and 151 controls, 60 with high-grade SILs and 240 controls, and 13 with invasive cancer and 65 controls were enrolled in 3 case-control studies. Controls were chosen at random among the women without lesions, with a frequency matching for age and center. We used the PCR method for the detection of cervical HPV DNA and the restriction fragment length polymorphism analysis for HPV typing. HIV antibody testing and CD4 cell count were performed. In multivariate analyses, factors associated with cervical lesions were: for low-grade SILs, HPV positivity, HIV-1 seropositivity and parity >3; for high-grade SILs, HPV positivity, chewing tobacco, HIV-1 seropositivity and illiteracy, and for invasive cancer, HPV positivity only. We found a diversity of HPV types associated with SILs. In HIV-1-infected women, SILs occurred at an early stage of HIV disease. Women infected with both HIV-1 and HPV were at much higher risk of SILs than women infected with each of these 2 viruses separately. Invasive cancer was linked to HIV-2 infection in univariate analysis only. Our results suggest that the relation of SILs with HIV-1 infection is mainly explained by HPV infection and that HIV-1-infected African women may not often reach the invasive stage of cervical cancer.

Treating systemic malignancies requires specialist skill and experience, with active treatment often providing the best initial palliation of symptoms. A full management plan involving general practitioner, patient and others is essential at this stage of HIV disease.

A retrospective study of the results of cervical cytological screening of HIV-infected women attending an inner city ambulatory HIV clinic over a 6-year period between 1987 and 1992 was carried out. During this time a total of 165 HIV-infected women attended for management of their HIV disease. The results of cervical cytological specimens (smears) were available in 136 (82.4%) women. The risk categories for HIV infection of these 136 women were intravenous drug use 110 (80.9%), heterosexual sex 24 (17.6%) and undetermined 2 (1.5%). Eighty-five (62.5%) of the 136 women were classified CDC group 2, 30 (22%) CDC group 3, and 21 (15.5%) CDC group 4 at the time of initial cytological screening. Forty-one (30.1%) women had mild dysplasia/CIN 1, 21 (15.4%) had moderate dysplasia/CIN 2 and 17 (12.5%) had severe dysplasia/CIN 3. The overall prevalence of dysplasia/CIN was 58.1%. Twenty-seven (34.2%) of the women with dysplasia/CIN had cytological evidence of human papillomavirus infection. No association between the clinical stage of HIV disease and the presence or degree of dysplasia/CIN was demonstrated. Women with cytological evidence of CIN were significantly more likely to have had genital warts than those with no evidence of CIN (OR 3.1, CI 1.1-10). In those women with cervical dysplasia who underwent colposcopic examination, CIN was confirmed in a high proportion of cases. The default rate from colposcopy, however, was high (35.4%).

Objective: To study a geographically defined population of women exposed to a drug-related risk for human immunodeficiency virus (HIV), together with carefully matched neighbourhood controls, in order to examine (1) the proportion of different groups having cervical cytopathology screening; (2) the association between HIV infection and cervical intraepithelial neoplasia; (3) the independent effect of CD4+ lymphocyte count and duration of HIV infection; and (4) the correspondence between cervical cytopathology and colposcopically directed biopsy., Design: A population-based study., Subjects: All women domiciled in Lothians with the following characteristics: between 1983 and 1987 they had a history of injection drug use or a seropositive partner with a history of injection drug use; they had a pregnancy after that exposure where their serostatus was known. In addition, neighbourhood controls were identified by computer matching for the following criteria--post-code sector, housing deprivation score, age, parity, pregnancy outcome, ethnic group, year of pregnancy, smoking., Main Outcome Measures: Search was carried out for the cervical smear nearest in time to the index pregnancy end date, providing serostatus was known at that time. All identified smears were assessed by a cytopathologist without knowledge of clinical information, study group or serostatus., Results: Of 376 women, appropriate cervical smears were identified for 336. The proportions screened in the different groups were similar. There were more abnormal smears in the seropositive group than in the drug-related seronegative (P < 0.01) or the neighbourhood control groups (P < 0.001). HIV-infected women with abnormal smears had lower CD4+ lymphocyte counts (P < 0.0005). There was a reasonable correspondence between cytopathological classification and histological grading, and this was of similar strength in cases and controls (weighted kappa 0.72, 0.74)., Conclusions: There is a definite relation between HIV infection and cervical intraepithelial neoplasia. This is related to immune depletion but whether this is the sole mechanism for the association is unclear.

Objective: To review the current literature on cervical disease (dysplasia, cervical intraepithelial neoplasia [CIN] or carcinoma) in women with HIV infection and to assess recommendations for cervicovaginal screening in these patients., Data Sources: MEDLINE and AIDSLINE were searched for relevant articles published in English or French between January 1987 and February 1993, abstracts presented at international AIDS conferences from 1989 to 1993 were evaluated, and pertinent agencies and organizations were consulted., Study Selection: A total of 92 reports of gynecologic disease in women with HIV infection were examined; 32 studies were retained that reported pertinent findings on cervical dysplasia, CIN or cervical carcinoma., Data Extraction: The following criteria were used to extract data: study design (descriptive v. comparative), sample size, heterogeneity of the study population, presence of immunodeficiency indicators (i.e., absolute CD4+ lymphocyte count) and presence of concomitant vaginal infections. Recommendations were assessed for their specific application to women with HIV infection., Data Synthesis: Data on the associations between stage of cervical disease and response to treatment at varying levels of CD4+ lymphocyte depletion were incomplete. Recommendations by official bodies for cervicovaginal screening in women with HIV infection differed little from recommendations for standard care of all women of reproductive age., Conclusions: The consequences of a missed or delayed diagnosis of cervical disease for women with HIV infection can be severe. Pending further research, more frequent cervicovaginal screening through Papanicolaou testing and colposcopy in women with HIV infection is warranted.